DC regulation of T cell immunity within the lymph nodes
This project is focused on delineating the factors that control rDC programming in the lungs and how the type and degree of the pulmonary infection is translated by rDC into different effector programming of T cells within the lymph nodes. Our work has shown that the degree of influenza virus infection leads to diverse programming of rDC which in turn results in differential DC cytokine production in the lymph nodes and distinct levels of T cell fitness. Specifically we have defined a novel pathway controlling the level of T cell immunity during lethal influenza virus infections. During highly pathogenic influenza infections DC recognize IL-12 p40 within the lymph nodes leading to upregulation of FasL on their cell surface. As naïve influenza-specific T cells are activated they upregulates Fas. Subsequent interaction of FasL with Fas leads to a death of the T cells resulting in T cell lymphopenia- a feature that is a hallmark of H5N1 influenza virus infections in humans.